- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Males and females with SMA type II or type III, aged 18 to 70 years at the time of enrollment.
- Genetic documentation of 5Q SMA homozygous gene deletion, mutation, or compound heterozygote.
- Are treatment naïve for SPINRAZA® (nusinersen).
- Have been prescribed SPINRAZA® (nusinersen) by the treating physician as part of their clinical care for SMA following the FDA approved prescribing information guidelines as follows: dose level (12 mg), dosing schedule (3 loading doses administered at 14-day intervals, and the fourth loading dose administered 30 days after the third dose and subsequent maintenance doses administered every 4 months) and safety lab monitoring (CBC, PT, INR, PTT, UA) done prior to each dose administration.
- Believed to be able to complete all study procedures, measurements and visits.
- Estimated life expectancy at least 30 months from first dosing, in the opinion of the Investigator.
- Revised upper limb module (RULM) score ≥ 4 (more than marginal upper extremity function/strength.
- Must meet either Group 1 or Group 2 criteria.
For Group 1 subjects:
- May be ambulatory or non-ambulatory (defined as being wheelchair reliant at least 75% of time and unable to walk at least 10 meters without assistance).
- RULM score of 4-34, inclusive.
For Group 2 subjects:
- Ability to walk at least 10 meters without assistance (i.e., four point walking aid).
- Be free of major orthopedic deformities that limit ambulation.
- An ambulatory subject can qualify for both Group 1 and Group 2 if the RULM score is ≤
- Revised upper limb score ≤ 3.
- Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for >16 hours during a 24-hour period, at screening.
- Hospitalization for major medical event including: surgery (i.e., scoliosis surgery, other surgery), cardiac event, pulmonary event, or other major medical problem within 2 months of screening or planned major surgical procedure likely to impact the clinical assessments during the duration of the study. Outpatient surgical procedure (i.e., placement of feeding tube) is not considered an exclusionary major medical event.
- Presence of a symptomatic severe active infection or illness during the screening period that is likely to impact the performance on the clinical assessments.
- Prior exposure to SPINRAZA® (nusinersen).
- Prior disorder, injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the subject's ability to perform any of the outcome measure testing required in the protocol and from which the subject has not fully recovered or achieved a stable baseline.
- Treatment with an investigational drug (e.g., oral albuterol/salbutamol, riluzole, carnitine, creatine, sodium phenylbutyrate, etc.), biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer.Patients using intrathecal drug delivery devices, including investigational devices with an active IDE designation in the United States, may be eligible but require Study PI approval prior to enrollment.
- Any history of exposure to gene therapy, antisense oligonucleotide therapy, or cell transplantation that was intended for the treatment of SMA.
- Ongoing medical condition that according to the Clinical Center Investigator would interfere with the conduct and assessments of the study. Examples are medical disability (e.g., wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromise the ability of the subject to undergo study procedures.